Ethyl 2-butynoate → HCID 71254826, compound

HRID 1508342Notes

Reaction equation

HRID 1508342 reaction equation
[Cl:1][C:2]1[C:3]([F:19])=[C:4]([C:8]2[C:12]([CH3:13])=[C:11]([C:14]([O:16]CC)=[O:15])[O:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(OCC)(=O)C#CC>C(#N)C>[Cl:1][C:2]1[C:3]([F:19])=[C:4]([C:8]2[C:12]([CH3:13])=[C:11]([C:14]([OH:16])=[O:15])[O:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 78043Ethyl 2-butynoateHCID 71254992HCID 71254992, compound

Product 1

HCID 71254826HCID 71254826, compoundYield 2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 3-(3-chloro-2-fluorophenyl)-4-methylisoxazole-5-carboxylate: Ethyl but-2-ynoate (0.725 ml, 6.22 mmol) and Intermediate 46A (0.36 g, 2.074 mmol) were dissolved in acetonitrile (10.37 mL). Magtrieve (1.742 g, 20.74 mmol) was added and the reaction mixture was stirred in a sealed tube at 80° C. After 2 h, the reaction was cooled to rt and then it was filtered through CELITE®, rinsing with EtOAc. The filtrate was concentrated and purified by reverse phase HPLC to afford the desired product (0.009 g, 2% yield) as a white solid. MS(ESI) m/z: 284.0 (M+H)+. 1H NMR (500 MHz, MeOD) δ 7.70 (ddd, J=8.0, 7.2, 1.7 Hz, 1H), 7.49 (ddd, J=7.8, 6.3, 1.7 Hz, 1H), 7.35 (td, J=7.8, 1.1 Hz, 1H), 4.46 (q, J=7.2 Hz, 2H), 2.25 (d, J=1.9 Hz, 3H), 1.42 (t, J=7.2 Hz, 3H) ppm. The other regioisomer, ethyl 3-(3-chloro-2-fluorophenyl)-5-methylisoxazole-4-carboxylate (0.083 g, 14%) was also obtained as a colorless oil. MS(ESI) m/z: 284.0 (M+H)+.

Workup

  1. additionMagtrieve (1.742 g, 20.74 mmol) was added
  2. temperaturethe reaction was cooled to rt
  3. filtrationit was filtered through CELITE®
  4. washrinsing with EtOAc
  5. concentrationThe filtrate was concentrated
  6. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-0a5416dd9893493dadb248a4b6670e05
Source dataset
uspto-grants-2015_12
Patent number
US09221818B2

Reaction notes

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